Hair cells in the chick cochlear duct exhibit a precise basal-to- apical gradient in the length, width and number of their stereocilia. In other vertebrates, these gradients have been shown to play an important role in determining the frequency tuning of individual hair cells and they are presumed to have a similar function in the chick cochlea. If the morphology of the stereociliary bundle does contribute to the frequency tuning of a hair cell, then it becomes important to understand how a hair cell at each position along the cochlear duct "knows" what the mature size and shape of its bundle should be. Moreover, it needs to be determined how a bundle of the appropriate size is established during embryonic development and how the growth of the bundle correlates with the maturation of the synaptic connections and functional activity of the hair cell. In addition, studies of stereocilia development are important for understanding how regeneration hair cells are produced in the chick cochlea following acoustic damage. Recent studies indicate that new hair cells replace those that have been lost in noise-damaged cochlea and that this replacement occurs by a process which is identical to that of hair cell development in the embryo. The long-term objectives of this project are to understand 1) how the development of the stereociliary bundle correlates with development of the transduction mechanism and the establishment of fine frequency tuning in individual hair cells; and 2) how hair cell regeneration is stimulated in the mature cochlear epithelium and whether the newly-formed hair cells are capable of re-establishing functional neural connections. The experiments on stereocilia development and regeneration will be analyzed with scanning and transmission electron microscopy and video- enhanced differential-interference-contrast light microscopy. The questions addressed in this research project could have a bearing on our understanding of the mechanism behind the development of hair cell structure and function and the potential for cochlear hair cell regeneration to ameliorate sensori-neural hearing loss.